Chiral platinum complex, method for preparing the same, and method for using the same

ABSTRACT

A method for synthesizing the chiral platinum complex (I), includes: dissolving 0.700 g of Pt(DMSO)2(NO3)2 in 30 mL of dichloromethane as a solvent to yield a solution; adding 0.450 g of 1,4-(4R)-diphenyl-2-oxazolinyl benzene to the solution, and reflux a resulting mixture for reaction for 48 hrs, and stopping the reaction; filtrating reaction products; and adding dichloromethane and petroleum ether, and naturally volatilizing to yield a binuclear platinum complex single crystal. A method for condensation of benzophenone imine and trimethylsilitrile by using the chiral platinum complex as a catalyst. A method for treating cancer includes administering the chiral platinum complex to a patient in need thereof. The cancer includes: lung cancer (A549), nasopharyngeal carcinoma (KB), anti-drug-resistant nasopharyngeal carcinoma (KB-VIn), and human breast cancer (MCF-7).

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims the benefit of Chinese Patent Application No. 201911005978.6 filed Oct. 22, 2019, the contents of which are incorporated herein by reference.

BACKGROUND OF THE INVENTION Field of the Invention

The present application relates to a metal organic coordination compound (complex) and its preparation method, particularly to a platinum-containing metal organic complex and its preparation method, and more particularly to a crystal of a platinum oxazoline complex and its synthetic method.

Description of the Related Art

Metal platinum complex has attracted wide attention due to its potential application value in anti-cancer, molecular magnet, fluorescent material and so on. There have been a lot of literature reports on the synthetic method of metal-platinum complex during recent years.

1. Cis/trans influences in platinum (II) complexes. X-ray crystal structures of cis-dichloro (dimethyl sulfide) (dimethyl sulfoxide) platinum (II) and cis-dichloro (dimethyl sulfide) (dimethyl phenyl phosphine) platinum (II), Journal of Molecular Structure, 470, 1-2, 39-47.

2. Design of chiral macrocyclic complexes based on trans-chelation of n:n metal-bidentate P, N- or N, N-ligands, Chemistry Letters (2006), 35, (2), 172-173.

SUMMARY

It is an objective of the present application to provide a Pt—N metal organic complex for application in the catalytic field, in order to solve the technical problem of selection as ligands and synthesis of a zinc complex.

To achieve the above objective, in accordance with one embodiment of the present application, there is provided a platinum complex. The platinum complex is a complex having a chemical formula (I) and prepared from dimethyl sulfoxide platinum nitrate and 1,4-(4R)-diphenyl-2-oxazolinyl benzene:

Chemical name: [1,4-(4R)-diphenyl-2-oxazolinyl benzene] platinum nitrate complex, referred to as complex (I).

In accordance with another embodiment of the present application, there is provided a method for synthesizing the above-described chiral complex (I), comprising: reaction, separation, and purification. The method specifically comprises: dissolving 0.700 g of Pt(DMSO)₂(NO₃)₂ in 30 mL of dichloromethane and 20 mL of chlorobenzene as a solvent to yield a solution; adding 0.450 g of 1,4-(4R)-diphenyl-2-oxazolinyl benzene to the solution, and reflux a resulting mixture for reaction for 48 hrs, and stopping the reaction; filtrating reaction products; and adding dichloromethane and petroleum ether, and naturally volatilizing to yield a binuclear platinum complex single crystal.

In accordance with still another embodiment of the present application, there is provided a method for condensation of benzophenone imine and trimethylsilitrile by using the above-described chiral platinum complex as a catalyst. The complex shows excellent catalytic performance in the reaction of benzophenone imine and trimethylsilitrile, and its conversion rate is up to 99%.

In accordance with still another embodiment of the present application, there is provided a method for treating cancer comprising administering the chiral platinum complex of claim 1 to a patient in need thereof, wherein the cancer comprises: lung cancer (A549), nasopharyngeal carcinoma (KB), anti-drug-resistant nasopharyngeal carcinoma (KB-VIn), and human breast cancer (MCF-7).

The method for synthesizing the above-described chiral complex according to an embodiment of the present application can achieve one-step reaction to yield the target product. The process is simple and easy to operate.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is an X-ray diffraction analysis drawing of binuclear platinum complex crystal;

FIG. 2 is a NMR spectrogram of binuclear platinum complex crystal;

FIG. 3 is a nuclear magnetic carbon spectrum of binuclear platinum complex crystal.

DETAILED DESCRIPTION OF THE EMBODIMENTS

1. Platinum Bichloride and Dimethyl Sulfoxide Complex

1.2042 g of platinum bichloride, 10 mL of DMSO, and 30 mL of dichloromethane were added to a 100 mL two-mouth flask to yield a mixture. The mixture was refluxed for 60 hrs, the reaction was stopped, and a resulting reaction mixture was stood. A solid dimethyl sulfoxide platinum complex was obtained with a yield thereof being 45%.

Elemental analysis results were as follows:

Test values: C: 11.78%, H: 2.91%;

Calculated values: C: 11.38%, H: 2.86%, IR (KBr): 1157, 1134, 450, 430.

2. Dimethyl Sulfoxide and Platinum Nitrate Complex

To a two-mouth flask, 0.3521 g of dimethyl sulfoxide platinum chloride, 0.5135 g of silver nitrate, and 20 mL of dichloromethane as solvent, were added for carrying out reaction in dark by using an aluminum foil at room temperature for 30 hrs. A resulting reaction mixture was filtrated and added with dichloromethane/trichloromethane in a volume ratio of 1/1 to prepare a solution. The resulting solution was naturally volatilized to obtain a dimethyl sulfoxide platinum nitrate complex in a solid form, with a yield thereof being 42%.

3. Preparation of Dimethyl Sulfoxide Binuclear Platinum Complex Crystal

0.700 g of Pt(DMSO)₂(NO₃)₂ were taken and dissolved with 30 mL of dichloromethane as the solvent to yield a resulting solution. 0.450 g of 1,4-(4R)-diphenyl-2-oxazolinyl benzene was added to the resulting solution for reflux reaction for 48 hrs. The reaction was stopped. Thereafter, reaction products were filtrated, and added with dichloromethane and petroleum ether, and naturally volatilized, to obtain a new single crystal of binuclear platinum complex, with a yield thereof being 90%, m.p.121-122° C.; [α]5D=+125.0° (c 0.04, DMF). Elemental analysis: C156H144N24048Pt6: Test values: C, 43.90, H, 3.71, N, 7.51; Calculated values: (%) C, 43.64, H, 3.38, N, 7.83; ¹H NMR (600 MHz, DMSO), δ ppm 7.95 (s, 8H, ArH), 7.12-7.32 (m, 20H, ArH), 4.56-4.64 (m, 4H, CH), 4.45-4.49 (m, 4H, CH), 4.16 (t, J=7.9 Hz, 4H, CH), 3.04 and 3.02 (dd, J=6.1, 6.8 Hz, 4H, 2×CH2), 2.85 and 2.82 (dd, J=7.3, 7.3 Hz, 4H, 2×CH2); 13C NMR (150 MHz, DMSO) 162.7, 138.5, 130.4, 129.8, 128.8, 128.6, 126.8, 72.3, 67.8, 41.3; ν_(max) (cm⁻¹) 3448, 3026, 2924, 2854, 2426, 1645, 1610, 1571, 1510, 1497, 1454, 1384, 1281, 1259, 1084, 1063, 1015, 967, 919, 861, 839, 756, 728, 699;

The data of the complex crystal are as follows:

Empirical formula: C156H144N24O48Pt6

Molecular weight: 4293.49

Temperature: 293.19(10)K

Wavelength: 1.54184 Å

Crystal system, spatial group: Monoclinic system, C2

crystal cell parameters: a=33.373 Å; α=90°.

b=9.580(3) Å; β=118.303(6°).

c=32.316 (9) Å; γ=90°.

Volume: 9096 (4) Å {circumflex over ( )}3

Electric density: 2, 1.380 Mg/m{circumflex over ( )}3

Absorption, correction parameter: 4.696 mm{circumflex over ( )}-1

Number of electrons in a single cell: 3682.0.0

Crystal size: 0.20×0.12×0.06 mm

Theta angle range: 4.472 to 50

Index collection range of HKL: −39<=h<=39, −11<k<11, −38<l<=38

Collect/Independent diffraction data: 16001/4652[R(int)=0.0752]

Method of absorption correction: Multilayer scanning

Method used for refinement: Least square method of matrix of F{circumflex over ( )}2

Number of data/number of use limit/number of parameters: 4652/499//803

Method used for refinement: 0.995

Coincidence factor for diffraction point: R1=0.0902, ωR2=0.2485

Coincidence factor of observable diffraction: R1=0.1416, ωR2=0.2892

Maximum peak and valley on the difference Fourier diagram: 1.00 and −2892 e.Å{circumflex over ( )}-3

Typical Bond Length Data for Crystal are Listed as Follows:

Atom Atom Length/Å C₁ C₄ 1.42(3) C₁ N₁ 1.36(3) C₁ O₁ 1.30(2) C₂ C₃ 1.58(3) C₂ O₁ 1.37(3) C₃ C₂₀ 1.56(3) C₃ N₁ 1.53(2) C₄ C₅ 1.42(3) C₄ C₉ 1.34(3) C₅ C₆ 1.29(3) C₆ C₇ 1.51(3) C₇ C₈ 1.20(3) C₇ C₁₀ 1.49(3) C₈ C₉ 1.51(3) C₁₀ N₃ 1.29(3) C₁₀ O₃ 1.33(2) C₁₁ C₁₂ 1.61(2) C₁₁ O₃ 1.55(2) C₁₂ C₁₃ 1.39(3) C₁₂ N₃ 1.48(2) C₁₃ C₁₄ 1.47(2) C₁₄ C₁₅ 1.3900 C₁₄ C₁₉ 1.3900 C₁₅ C₁₆ 1.3900 C₁₆ C₁₇ 1.3900 C₁₇ C₁₈ 1.3900 C₁₈ C₁₉ 1.3900 C₂₀ C₂₁ 1.53(2) C₂₁ C₂₂ 1.3900 C₂₁ C₂₆ 1.3900 C₂₂ C₂₃ 1.3900 C₂₃ C₂₄ 1.3900 C₂₄ C₂₅ 1.3900 C₂₅ C₂₆ 1.3900 C₂₇ C₂₈ 1.46(3) C₂₇ C₄₆ 1.53(3) C₂₇ N₂ 1.47(3) C₂₈ O₂ 1.38(3) C₂₉ C₃₀ 1.40(3) C₂₉ N₂ 1.36(3) C₂₉ O₂ 1.34(2) C₃₀ C₃₁ 1.37(3) C₃₀ C₃₅ 1.46(3) C₃₁ C₃₂ 1.46(3) C₃₂ C₃₃ 1.41(3) C₃₃ C₃₄ 1.37(3) C₃₃ C₃₆ 1.53(3) C₃₄ C₃₅ 1.25(3) C₃₆ N₄ 1.29(3) C₃₆ O₄ 1.26(3) C₃₇ C₃₈ 1.47(3) C₃₇ O₄ 1.35(2) C₃₈ C₃₉ 1.66(3) C₃₈ N₄ 1.43(3) C₃₉ C₄₀ 1.59(2) C₄₀ C₄₁ 1.3900 C₄₀ C₄₅ 1.3900 C₄₁ C₄₂ 1.3900 C₄₂ C₄₃ 1.3900 C₄₃ C₄₄ 1.3900 C₄₄ C₄₅ 1.3900 C₄₆ C₄₇ 1.49(2) C₄₇ C₄₈ 1.3900 C₄₇ C₅₂ 1.3900 C₄₈ C₄₉ 1.3900 C₄₉ C₅₀ 1.3900 C₅₀ C₅₁ 1.3900 C₅₁ C₅₂ 1.3900 N₁ Pt₁ 2.141(18) N₂ Pt₁ 2.025(14) N₃ Pt₂ 2.080(16) N₄ Pt₂ 2.152(13) C₅₃ C₆₇ ¹ 1.44(8) C₅₃ N₅ 1.19(4) C₅₃ O₅ 1.42(4) C₅₄ C₅₅ 1.73(5) C₅₄ O₅ 1.38(5) C₅₅ C₅₆ 1.61(3) C₅₅ N₅ 1.45(4) C₅₆ C₅₇ 1.32(3) C₅₇ C₅₈ 1.3900 C₅₇ C₆₂ 1.3900 C₅₈ C₅₉ 1.3900 C₅₉ C₆₀ 1.3900 C₆₀ C₆₁ 1.3900 C₆₁ C₆₂ 1.3900 C₆₃ C₆₄ 1.60(3) C₆₃ N₆ 1.36(4) C₆₃ O₆ 1.43(4) C₆₄ C₆₅ 1.3900 C₆₄ C₆₉ 1.3900 C₆₅ C₆₆ 1.3900 C₆₆ C₆₇ 1.3900 C₆₇ C₅₃ ¹ 1.44(4) C₆₇ C₆₈ 1.3900 C₆₈ C₆₉ 1.3900 C₇₀ C₇₁ 1.51(3) C₇₀ O₆ 1.42(2) C₇₁ C₇₂ 1.38(4) C₇₁ N₆ 1.45(4) C₇₂ C₇₃ 1.36(4) C₇₃ C₇₄ 1.3900 C₇₃ C₇₈ 1.3900 C₇₄ C₇₅ 1.3900 C₇₅ C₇₆ 1.3900 C₇₆ C₇₇ 1.3900 C₇₇ C₇₈ 1.3900 N₅ Pt₃ 1.99(3) N₆ Pt₃ 2.09(2) N₇ O₇ 1.09(3) N₇ O₈ 1.24(3) N₇ O₉ 1.29(3) ¹−X, +Y, −Z

Typical Bond Angle Data for Crystal are Listed as Follows:

Atom Atom Atom Angle/° Atom Atom Atom Angle/° N₁ C₁ C₄ 126.5(18) C₅₂ C₄₇ C₄₆ 118.1(12) O₁ C₁ C₄ 121.9(17) C₄₇ C₄₈ C₄₉ 120.0 O₁ C₁ N₁ 111.6(17) C₅₀ C₄₉ C₄₈ 120.0 O₁ C₂ C₃ 104.6(17) C₄₉ C₅₀ C₅₁ 120.0 C₂₀ C₃ C₂ 108.5(19) C₅₂ C₅₁ C₅₀ 120.0 N₁ C₃ C₂ 100.0(17) C₅₁ C₅₂ C₄₇ 120.0 N₁ C₃ C₂₀ 106.5(14) C₁ N₁ C₃ 108.4(16) C₁ C₄ C₅ 116.8(17) C₁ N₁ Pt₁ 126.7(13) C₉ C₄ C₁ 120.8(19) C₃ N₁ Pt₁ 124.9(13) C₉ C₄ C₅ 122.2(19) C₂₇ N₂ Pt₁ 128.5(13) C₆ C₅ C₄ 121.1(19) C₂₉ N₂ C₂₇ 102.2(16) C₅ C₆ C₇ 118(2) C₂₉ N₂ Pt₁ 128.8(13) C₈ C₇ C₆ 119.8(18) C₁₀ N₃ C₁₂ 109.5(15) C₈ C₇ C₁₀ 122.6(17) C₁₀ N₃ Pt₂ 126.9(11) C₁₀ C₇ C₆ 117.6(16) C₁₂ N₃ Pt₂ 123.1(11) C₇ C₈ C₉ 124.3(19) C₃₆ N₄ C₃₈ 102.6(16) C₄ C₉ C₈ 114.0(19) C₃₆ N₄ Pt₂ 130.1(14) N₃ C₁₀ C₇ 127.9(15) C₃₈ N₄ Pt₂ 127.3(12) N₃ C₁₀ O₃ 119.3(16) C₁ O₁ C₂ O₃ C₁₀ C₇ 112.8(17) C₂₉ O₂ C₂₈ O₃ C₁₁ C₁₂ 101.6(12) C₁₀ O₃ C₁₁ C₁₃ C₁₂ C₁₁ 115.5(15) C₃₆ O₄ C₃₇ C₁₃ C₁₂ N₃ 115.1(14) N₂ Pt₁ N₁ N₃ C₁₂ C₁₁ 102.6(14) N₃ Pt₂ N₄ C₁₂ C₁₃ C₁₄ 115.2(16) N₅ C₅₃ C₆₇ ¹ C₁₅ C₁₄ C₁₃ 118.9(12) N₅ C₅₃ O₅ C₁₅ C₁₄ C₁₉ 120.0 O₅ C₅₃ C₆₇ ¹ C₁₉ C₁₄ C₁₃ 121.0(12) O₅ C₅₄ C₅₅ C₁₄ C₁₅ C₁₆ 120.0 C₅₆ C₅₅ C₅₄ C₁₇ C₁₆ C₁₅ 120.0 N₅ C₅₅ C₅₄ C₁₆ C₁₇ C₁₈ 120.0 N₅ C₅₅ C₅₆ C₁₉ C₁₈ C₁₇ 120.0 C₅₇ C₅₆ C₅₅ C₁₈ C₁₉ C₁₄ 120.0 C₅₆ C₅₇ C₅₈ C₂₁ C₂₀ C₃ 109.8(17) C₅₆ C₅₇ C₆₂ C₂₂ C₂₁ C₂₀ 119.8(13) C₅₈ C₅₇ C₆₂ C₂₂ C₂₁ C₂₆ 120.0 C₅₇ C₅₈ C₅₉ C₂₆ C₂₁ C₂₀ 120.2(13) C₆₀ C₅₉ C₅₈ C₂₁ C₂₂ C₂₃ 120.0 C₆₁ C₆₀ C₅₉ C₂₂ C₂₃ C₂₄ 120.0 C₆₀ C₆₁ C₆₂ C₂₅ C₂₄ C₂₃ 120.0 C₆₁ C₆₂ C₅₇ 120.0 C₂₄ C₂₅ C₂₆ 120.0 N₆ C₆₃ C₆₄ 130(2) C₂₅ C₂₆ C₂₁ 120.0 N₆ C₆₃ O₆ 124(2) C₂₈ C₂₇ C₄₆ 117.3(19) O₆ C₆₃ C₆₄ 104(2) C₂₈ C₂₇ N₂ 106.9(18) C₆₅ C₆₄ C₆₃ 115.8(18) N₂ C₂₇ C₄₆ 107.7(17) C₆₅ C₆₄ C₆₉ 120.0 O₂ C₂₈ C₂₇ 107.6(18) C₆₉ C₆₄ C₆₃ 123.4(18) N₂ C₂₉ C₃₀ 120.9(18) C₆₆ C₆₅ C₆₄ 120.0 O₂ C₂₉ C₃₀ 121.3(19) C₆₅ C₆₆ C₆₇ 120.0 O₂ C₂₉ N₂ 116.9(18) C₆₆ C₆₇ C₅₃ ¹ 119(2) C₂₉ C₃₀ C₃₅ 121.5(19) C₆₈ C₆₇ C₅₃ ¹ 120(2) C₃₁ C₃₀ C₂₉ 116.9(19) C₆₈ C₆₇ C₆₆ 120.0 C₃₁ C₃₀ C₃₅ 118.9(19) C₆₉ C₆₈ C₆₇ 120.0 C₃₀ C₃₁ C₃₂ 117.5(18) C₆₈ C₆₉ C₆₄ 120.0 C₃₃ C₃₂ C₃₁ 119.1(18) O₆ C₇₀ C₇₁ 112(3) C₃₂ C₃₃ C₃₆ 114.4(18) C₇₂ C₇₁ C₇₀ 118(3) C₃₄ C₃₃ C₃₂ 117.5(18) C₇₂ C₇₁ N₆ 114(3) C₃₄ C₃₃ C₃₆ 127.9(19) N₆ C₇₁ C₇₀ 106(3) C₃₅ C₃₄ C₃₃ 126.2(19) C₇₃ C₇₂ C₇₁ 131(3) C₃₄ C₃₅ C₃₀ 119.3(19) C₇₂ C₇₃ C₇₄ 118.3(19) N₄ C₃₆ C₃₃ 121(2) C₇₂ C₇₃ C₇₈ 121.0(19) O₄ C₃₆ C₃₃ 119(2) C₇₄ C₇₃ C₇₈ 120.0 O₄ C₃₆ N₄ 120(2) C₇₅ C₇₄ C₇₃ 120.0 O₄ C₃₇ C₃₈ 105.4(16) C₇₄ C₇₅ C₇₆ 120.0 C₃₇ C₃₈ C₃₉ 108.9(19) C₇₇ C₇₆ C₇₅ 120.0 N₄ C₃₈ C₃₇ 104.9(18) C₇₆ C₇₇ C₇₈ 120.0 N₄ C₃₈ C₃₉ 104.6(17) C₇₇ C₇₈ C₇₃ 120.0 C₄₀ C₃₉ C₃₈ 114.9(16) C₅₃ N₅ C₅₅ 107(3) C₄₁ C₄₀ C₃₉ 120.8(12) C₅₃ N₅ Pt₃ 129(2) C₄₁ C₄₀ C₄₅ 120.0 C₅₅ N₅ Pt₃ 124(2) C₄₅ C₄₀ C₃₉ 119.2(12) C₆₃ N₆ C₇₁ 100(2) C₄₀ C₄₁ C₄₂ 120.0 C₆₃ N₆ Pt₃ 130.3(17) C₄₁ C₄₂ C₄₃ 120.0 C₇₁ N₆ Pt₃ 128(2) C₄₂ C₄₃ C₄₄ 120.0 C₅₄ O_(S) C₅₃ 101(3) C₄₅ C₄₄ C₄₃ 120.0 C₇₀ O₆ C₆₃ 96(2) C₄₄ C₄₅ C₄₀ 120.0 N₅ Pt₃ N₆ 176.0(11) C₄₇ C₄₆ C₂₇ 117.0(17) O₇ N₇ O₈ 126(3) C₄₈ C₄₇ C₄₆ 121.6(12) O₇ N₇ O₉ 123(2) C₄₈ C₄₇ C₅₂ 120.0 O₈ N₇ O₉ 104(3) ¹−X, +Y, −Z

Condensation Reaction Between Benzophenone Imine and Trimethylsilitrile

0.025 mL of benzophenone imine and 0.4 mL of trimethylsilitrile was taken and added to a 25 mL small flask, then, 1 mL of THF and 0.0157 g of the compound I were added, and stirred at room temperature for 8 hrs. A small number of the sample was taken for nuclear magnetic detection. The conversion rate was more than 99%; ¹H NMR (600 MHz, CDCl₃, 27° C.), δ7.23-7.59 (m, 10H), 4.10 (s, 2H).

Application of Anti-Cancer Activity

Platinum complex designed and synthesized according to the structure of the active natural product in the present application exhibits strong inhibitory activity (ED₅₀<10.0 μg/mL) for the treatment of A549 (lung cancer), KB (nasopharyngeal carcinoma), KB-VIn (anti-drug-resistant nasopharyngeal carcinoma) and human breast cancer (MCF-7). Therefore, it is expected that this compound can be used to treat various kinds of cancers, including lung cancer, breast cancer, oral cancer cells, and breast cancer cells. Part of this compound's anti-cancer activity test results are listed in Table 1:

TABLE 1 Anti-cancer Activity Data of Platinum Complex (I) Cell line Human lung cancer Human oral cancer cells Human breast cancer cells Human breast cancer A549 cell MDA-MB-231 KB-VIN cell MCF-7 Average Standard Average Standard Average Standard Average Standard Sample value deviation value deviation value deviation value deviation Platinum complex 6.12 ±0.22 6.92 ±0.13 4.06 ±0.13 2.43 ±0.02 (I) Cisplatin 4.96 ±0.09 26.41 ±0.74 3.01 ±0.07 29.99 ±0.93 

1. A chiral platinum complex having a chemical formula (I):


2. The chiral platinum complex of claim 1, wherein the chiral platinum complex has crystal cell parameters as follows: a=33.373 Å α=90°, b=9.580(3) Å β=118.303(6°), c=32.316(9) Å γ=90°, measured at a temperature of 293.19 (10) K on an Oxford X-ray single crystal diffractometer using a monoclinic system, C2, which is monochromatized by a graphite monochromator.
 3. (canceled)
 4. A method for condensation of benzophenone imine and trimethylsilitrile by using the chiral platinum complex of claim 1 as a catalyst.
 5. A method for treating cancer comprising administering the chiral platinum complex of claim 1 to a patient in need thereof, wherein the cancer comprises: lung cancer (A549), nasopharyngeal carcinoma (KB), anti-drug-resistant nasopharyngeal carcinoma (KB-VIn), and human breast cancer (MCF-7). 